Individual blood-brain barrier phenylalanine transport in siblings with classical phenylketonuria.

Recent studies indicate that individual blood-brain transport characteristics of phenylalanine may lead to different clinical outcomes in phenylketonuria (PKU) patients in spite of comparable dietary control. To check these preliminary data, we investigated four pairs of siblings with classical PKU (and identical genotype) using in vivo nuclear magnetic resonance spectroscopy in the course of an oral phenylalanine load (100 mg/kg body weight). Patients' brain phenylalanine concentrations were different in spite of similar blood levels. Interindividual variations of the apparent transport Michaelis constant, Kt,app, ranged from 0.10 to 0.84 mmol/L. The ratio of the maximal transport velocity, Tmax, over the intracerebral consumption rate, Vmet, varied between 2.61 and 14.0. Siblings with lower values for Kt,app, higher values for Tmax/Vmet, and higher concurrent brain phenylalanine levels showed a lower IQ and a higher degree of cerebral white matter abnormalities. The results indicate that blood-brain barrier transport characteristics and the resultant brain phenylalanine levels are causative factors for the individual clinical outcome in PKU.